Building synthetic multicellular systems using bottom–up approaches

Abstract A grand challenge in bottom-up synthetic biology is the design and construction of synthetic multicellular systems using non-living molecular components. Abstracting key features of compartmentalisation, reaction and diffusion, and communication provides the blueprint for assembling synthetic multi-scale systems with emergent properties. The diverse range of chemistries for building encapsulated reactions in micron-sized compartments offers combinatorial flexibility and modularity in building synthetic multicellular systems with molecular-level control. Here, we focus on recent advances in the emerging area of bottom-up approaches to create biologically-inspired multicellular systems. Specifically, we consider how intercellular communication and feedback loops can be integrated into populations of synthetic cells and summarise recent developments for the 2D/3D spatial localisation of micro-compartments. While building bottom-up multicellular systems is still in its infancy, progress in this field offers tractable models to understand the minimal requirements for generating multiscale systems from the molecular level for fundamental research and innovative technological applications.